Tumour infiltrating macrophages are capable of bone resorption

The cell types responsible for osteolysis associated with skeletal metastasis of solid malignancies are unclear. Tumour infiltrating macrophages (TIMs) isolated from primary mammary carcinomas of C3H/Avy mice were cultured on bone slices to assess their ability to resorb bone. After 14 days in co-culture with murine marrow stromal cell line ST2 and added 1,25-dihydroxyvitamin D3 and dexamethasone, TIMs showed increased tartrate-resistant acid phosphatase activity and formed numerous lacunar resorption pits. In the absence of ST2 cells, TIMs did not form lacunar resorption pits but produced roughening of the bone surface with exposure of mineralized collagen fibres. Normal alveolar macrophages, in both the presence and absence of ST2 cells similarly produced only surface resorption. TIMs are thus capable of both low-grade (surface) and high-grade (lacunar) pathological bone resorption, a specific interaction with stromal cells being necessary for the latter to occur. TIM-mediated bone resorption could account for different clinical and pathological patterns of tumour osteolysis.